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New work shows gut microbial taxa might vary, but function is stable in people with Crohn’s disease in remission

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The numbers, types, and functions of gut microbes and the molecules they produce vary greatly over time and between individuals; however, there is new evidence showing that the metabolic function these microbes perform is conserved in some cases. This new data comes from an analysis of the gut microbiome from several individuals with Crohn’s disease throughout a whole year. The study further showed that the conserved functions are redundant across multiple phyla in the gut microbiome and that gut microbiome metabolism is driven by a web of interconnected reactions and enzymes.

Research has revealed that the gut microbiome plays a fundamental role in our overall health. The microbiome is involved in several vital biological functions including, metabolism, digestion, and immunity. Scientists have shown that there is an enormous amount of variability in the species making up the gut microbiome of any one individual, and this variability is even greater in people with inflammatory bowel disease (e.g. Crohn’s disease).  This makes any investigation into why a microbiome is not functioning properly extremely difficult. To get around this, researchers posed the question of whether microbial composition was really the best way to seek answers.

The group carrying out this work included researchers from all over the US and included Microbiome Insights Scientific Advisory Board member Dr. Janet Jansson ofthe Pacific Northwest National Laboratory in Richland, Washington. Their approach was to focus on discrete “metabolic modules” within a gut microbiome instead of taxa or genetic relationships, the idea being that different bacteria can perform similar metabolic functions; so while two humans have a different make-up of species, their microbiomes on the whole could be functioning similarly. With this concept, the researchers wanted to tackle an open question in microbiome and inflammatory bowel disease (IBD) research—how does the observed volatility in the microbiome composition of patients with IBD influence the functions of the microbiome?

Fecal samples from individuals with Crohn’s following resection surgery and in remission were collected at 5 time points throughout a year and a dual metagenomics/metaproteomics approach applied: they used shotgun metagenomics sequencing to identify genes from the microbiome species and two-dimensional liquid chromatography tandem mass spectrometry to isolate the proteins. They found that the metaproteomes (the collections of proteins expressed by microbes in the samples) were highly personalized, meaning all the samples taken from an individual more closely resembled each other than they did any sample from another individual. There was, however, still a great deal of variability between the samples taken at different times from a single person. Next they identified “metabolic modules” of proteins known to be involved in certain pathways and functions. In doing so they observed that there were similar and redundant metabolic functions across the different phyla observed over time and between individuals. By further combing through the modules, a clear path from carbohydrate, lipid, and amino acid degradation to central metabolism and finally the production of fermentation products could be found.  According to the researchers, the modules show the interconnectedness of gut microbiome metabolism, meaning that the overall operation of the microbiome should be thought of as network focused on metabolic function.  

This study was not specifically designed to compare healthy vs. unhealthy individuals, says the research team, but because this population is known to have a wide range of taxonomic variability they were chosen to investigate how variation affects function. According to researchers, “the data revealed that microbiomes of these post-surgery individuals had significant variability in taxa, genes, and proteins; however, key metabolic modules associated with central metabolism were seen in all samples, even though the phyla of origin was often different.” Furthermore, they believe this approach provides a unique way to follow metabolic reactions and enzymes, even when the species and proteins involved vary. 

Blakeley-Ruiz JA, Erickson AR, Cantarel BL, et al. Metaproteomics reveals persistent and phylum-redundant metabolic functional stability in adult human gut microbiomes of Crohn’s remission patients despite temporal variations in microbial taxa, genomes, and proteomes. Microbiome. 2019; 7:18.

 

 

Microbiome Insights scientific advisory board member Curtis Huttenhower contributes to research identifying thousands of new human microbiome species

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Thousands of new microbial species making up the human microbiome have been identified from metagenome samples collected around the world. By reconstructing the microbial genomes found in over 9000 metagenome datasets, the microbial genomes of the unnamed species extend the knowledge of the human microbiome and should aid in development of future metagenomics technologies.

The work of identifying these new species was carried out by a team of researchers from Europe, New Zealand and the US, and included Harvard’s Dr. Curtis Huttenhower (a Microbiome Insights scientific advisory board member). The group used a scalable bioinformatics methodology to reconstruct the genomes of unknown bacteria found within the metagenome assemblies. Here the metagenome samples were site-specific human body samples (oral cavity, skin, vagina, and stool) from multiple people living all over the world. The diverse set included individuals of all ages, living varied lifestyles from 32 countries.

A wealth of information is contained in these samples, as they represent the whole-body microbiome of humans from different geographic locations that experience different climates and circumstances. Seven of the datasets also came from non-Westernized environments, further expanding the range of conditions the microbes are sampled from. Using these metagenomes as the starting point the researchers were able to apply their large-scale single-sample metagenomics assembly and identified 4930 species-level clades, 77% of which had no previous whole-genome level information.

Their method of assembly was optimized to maximize the quality of the microbial genomes being found in the metagenome sample, rather than the quantity. Despite this strict method, 154 723 new microbial genomes were identified, which more than doubles the current publicly available set of roughly 150 000 microbial genomes. With this investigation having doubled the catalogue of known microbial genomes, future studies attempting identify the contents of a metagenomics sample now have a more comprehensive reference set from which they can map out their samples. The metagenomics assembly strategies used in this work can also be applied to non-human associated metagenomes and will be applicable for new sequencing technologies such as synthetic or single molecule long read sequencing.

A large fraction of the previously unidentified species were seen in the non-Westernized samples; however, examples of the new species were prevalent throughout all samples. Roughly 2.5 million genes were also found within the known species-level clades, many of which were associated with conditions including infant development and Westernization. Several taxa of bacteria were found to be prevalent in this analysis despite not being observed in previous well-profiled populations. Still more taxa from underrepresented phyla, such as Saccharibacteria and Elusimicrobia, were found in oral and gut microbiomes.

According to the study authors, “the resulting genome set can thus serve as the basis for future strain-specific comparative genomics to associate variants in the human microbiome with environmental exposures and health outcomes across the globe.”

Pasolli E, Asnicar F, Manara S, et al. Extensive unexplored human microbiome diversity revealed by over 150,000 genomes from metagenomes spanning age, geography, and lifestyle. Cell. 2019; 176: 649-662.

 

 

 

Stanford group draws wide expertise from Microbiome Insights & others to complete Chan Zuckerberg Biohub’s Tabula Muris project

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A detailed database of transcriptomic data from over 100,000 individual cells taken from the mouse model organism Mus musculus, titled Tabula Muris, is now available for use by biomedical researchers around the world. This work, completed by the The Tabula Muris Consortium, was a project funded by the Chan Zuckerberg Biohub.

This database is the first concise and detailed collection of mouse single cell transcriptomic data from this important model organism. It reveals the individual gene expression levels of the cells from 20 different organs and tissues and is a first draft for an organism-wide representation of cellular diversity. This now-publicly-available resource will aid in the discovery of new cell types and of novel gene expression patterns, while also serving as a reference for healthy organs and tissues, making it an important baseline for future disease models. The team also made all of the data, scripts, and protocols publicly available along with an interactive data browser. The aim is to allow future groups to carry out further in depth-analysis and exact replications of their work.

In order to complete such an ambitious project, the consortium assembled expertise from several groups. Consortium members included researchers from Chan Zuckerberg Biohub, multiple faculty at Stanford University, and experts from the Palo Alto Healthcare System. Each group specialised in a tissue type (e.g. kidneys or lungs), or had specific experience (e.g. pathology or flow cytometry). A breadth of knowledge was required because the over 100,000 individual cells needed to be individually isolated. For mammalian cells, two methods were used: fluorescence-activated cell sorting and the microfluidic droplet technique. From here, DNA and RNA were extracted and sequenced. In tandem, fecal samples were collected for functional analysis of the microbiota. It was at this stage that Microbiome Insights provided their expertise by performing a customized suite of DNA extraction and library preparation services to contribute to the overall results.

“Working closely with Microbiome Insights to quickly analyze the data was critical to our ability to integrate microbiota information with the rest of the Cell Atlas project,” said KC Huang, a Stanford professor involved in the project. The sheer number of cell types and subsequent genomic information to be processed required an enormous feat of coordination—making this a remarkable example of research collaboration.

The strength of this single cell and organ approach is that it will allow researchers working with a single organ, for example, to see the changes that occur throughout the entire body. It provides a whole-body view of disease and development. This could aid in studies on prevention and potentially even cures for many important diseases such as diabetes, heart disease, and cancer. The Chan Zuckerberg group is now supporting a similar project, The Human Cell Atlas, which according to their website, is aimed at building “a collection of maps that will describe and define the cellular basis of health and disease”.

Global Engage 6th Microbiome R&D and Business Collaboration Forum Summary: Days 1 & 2

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Leaders in the microbiome industry met in San Diego (USA) for two days, on October 29th and 30th, 2018, to dive into the advancements in research and product development that have occurred to date. Microbiome Insights was an exhibitor at this event—The 6th Microbiome R&D and Business Collaboration Forum–one of the largest annual microbiome-related gatherings in the US, with 300 attendees coming from North America and Europe.

The conference talks were divided into three tracks: microbiome therapeutics, skin microbiome, and probiotics. Here, we present highlights from each of the tracks in this two-day event:

Day 1

Probiotics

Jennifer Spinler of Baylor College of Medicine spoke on “Targeting Antibiotic-Associated Digestive Diseases Using Next-Generation Probiotics”. She started by outlining the need for new therapies to prevent antibiotic-associated diarrhea. Clostridium difficile infection is one of the leading reasons for antibiotic administration, and a 2017 Cochrane Review showed probiotics can prevent Clostridium difficile-associated diarrhea in adults and children. Spinler’s approach is to explore a probiotic strategy for preventing Clostridium difficile infection in the first place by looking at how host bacteria are normally able to protect against C. difficile. She focused on Lactobacillus reuteri, which has anti-inflammatory effects and activity against Gram positive and Gram negative bacteria. She found that L. reuteri alone didn’t prevent the growth of C. difficile, but L. reuteri plus glycerol knocked down C. diff growth in the system—with an accompanying shift in the overall microbial community.

Brunella Gonzalez Cautela of Lallemand gave a talk on “Probio’Stick and the brain-gut axis: Focus on recent clinical findings”. She noted that the etiology of depression is obscure, but one contributor under consideration is immune-mediated inflammation. She thus posed the question: can probiotics be used for depression? A pilot study by the company, in collaboration with researchers from Queen’s University, focused on patients who were depressed but never treated before. In addition to completing a survey, the subjects were tested for inflammatory markers in the blood, serotonin levels, and fecal microbiome composition. Those who received ProbioStick for 8 weeks showed significant improvement in mood-related symptoms compared to those who received a placebo.

Microbiome

Kathy McCoy of University of Calgary presented on “Impact of the gut microbiome in shaping innate immunity: Defining Mechanisms”, going over several examples of using gnotobiotics to define mechanisms underlying microbiome and host interactions. In one example, researchers studied microbial impact on T Cells in a non-obese diabetic mouse model of type 1 diabetes. They looked at the ability of the bacteria to bring the integrase-specific T cells to the gut, and found that microbial antigens had a dramatic protective effect against colitis.

Jessica Schneider of Takeda Pharmaceuticals spoke about the company’s growing microbiome drug portfolio, and how gastrointestinal indications are paving the way for future indications (gut-brain axis and others). She explained the company’s interest in commensal bacterial co-occurrence networks in various disease states, and deriving effective therapeutics from these. Takeda is driven by the hypothesized mechanism of disease: either bugs as drugs, or (in the case of their collaboration with Enterome), drugs for/from bugs. She listed approaches in the industry, in increasing order of R&D complexity: fecal microbiota transplantation, bacteriophage engineering, bacterial consortia, engineered bacteria, single strain commensal bacteria, and small molecules.

Morten Isaksen of Bio-Me spoke on “Positioning microbiome analysis for use in precision medicine”. The company has developed a platform that does precision microbiome profiling (species/strain level) and direct quantification reads in less than a day. Isaksen described a demonstration study on diet: subjects consumed their normal diet for 4 weeks, then changed their diet in some way for the next 4 weeks—for example, consuming more fiber or changing sugar consumption. Bio-Me carried out daily sampling of fecal microbiota and found, interestingly, that after an initial microbiome change (after 3-5 days) there tended to be a rebound to pre-intervention levels of bacteria. Follow-up work will try to uncover the cause of this phenomenon.

Skin microbiome

Kausar Malik of Amway Corporation presented “The Cinco de Mayo Study: A one-year longitudinal study of the facial skin microbiome in normal healthy adults”—a project done in collaboration with the Microbiome Insights team. Malik described how bacterial species on the skin vary depending on the environment (e.g. moist or dry); the study aimed to find out the stability of the skin microbiome in a large population of healthy individuals over time, in order to begin identifying biomarkers of skin aging. In addition to skin swabs, they looked at red spots, wrinkles, brown spots, skin elasticity, barrier function, and surface pH. They found no significant change in alpha diversity over time, although some individuals showed a change in microbiome diversity on the cheek. Corynebacterium increased with age, and was also correlated with higher redness (in line with other published work).

Day 2

Microbiome

Eric Pamer of Memorial Sloan Kettering Cancer Center gave a keynote address on “Microbiota-mediated defense against intestinal infection”. His research focused on patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT): these patients receive antibiotics, chemotherapy, and radiation, and mortality is high in the case of bloodstream infection caused by vancomycin-resistant enterococcus (VRE). Given that the microbiome normally eliminates persistent VRE, the question is whether there’s a way to eliminate VRE in allo-HSCT patients. Pamer and colleagues showed that with a fecal transplant in these patients they re-established almost all the normal microbiome components—but which bugs were causing clearance of VRE? The researchers used particular bacteria and did a dilution test to examine the clearance of VRE. Blautia producta were the only bacteria that caused complete inhibition. When they looked into what Blautia producta expresses that none of the others do, they found it encodes a lantibiotic operon; these lantibiotics can also be expressed by anaerobes living in the colon.

Peter Spanogiannopoulos of UCSF was next up, with “The metabolism of fluoropyrimidine anticancer drugs by the human gut microbiome”. He cited work showing that Proteobacteria can inactivate 5FU—and noted that, fortunately, there is a lot about Proteobacteria in literature. He and his colleagues in the Turnbaugh lab are looking to answer the question: can probiotics rescue toxicity? One day they hope to sequence someone’s microbiome before administering anticancer drugs, in order to assess the pharmacokinetics.

Pierre Belichard of Enterome spoke on “Building the leading microbiome-derived immunotherapy company”. He explained that Enterome, a spin-out of MetaGenoPolis in France, is focused on determining function of the microbiome in cancer and inflammatory bowel disease. They are developing everything except ‘live biotics’—and their multiple programs are currently in various stages: for instance, glioblastoma and solid tumors (phase 1); Crohn’s disease (phase 2). They work on epitope mimicry to trigger an anti-tumor T-cell response, ‘waking up’ existing dormant T-cells in the gut lining to activate the biggest group of T cells in the human body. Their work in animal models has established this and they are now carrying it through in clinical trials with humans.

The next event in the microbiome track was a panel discussion led by Microbiome Insights CEO Malcolm Kendall: “Where the money is going and where the money will be made: The unique perspective of venture capitalists”. On the panel were Asish Xavier of J&J Innovation and Denise Kelly of Seventure. In response to an audience question, the panelists emphasized that they look carefully at every company that comes through the door; sometimes they ask for more information or progress and a company comes back later having secured a better position. Kendall asked the panelists the key things they look for in a company, and Kelly responded that the number one factor is top-notch science: validated and preferably peer-reviewed. Then comes intellectual property: who else is competing, and what makes the company different? Third is the business team and the research team. Xavier agreed, adding that the science may be very interesting but the key is whether it is translatable.

Timing is another factor: Xavier says he has seen companies take 20 years to bring something to market. He said timing is critical for a company—so sometimes he explores whether they can build a small product to bring to market while working on a larger one.

Kendall asked the panelists how they think microbiome science is progressing. Xavier acknowledged a lot of good science emerging—with an exponential number of publications—but not all of the ideas can be translated into a drug. The science only has potential as a company if you can get to phase 3 and beyond. Most times the drugs will be advanced by a bigger company because of regulatory challenges so the start-ups will have to partner at some point in their existence. Kelly agreed, and noted that over the past five years we have seen a massive capitalization of the scientific progress.

For more on the conference talks, see #MicrobiomeProbioticsForum on Twitter.

PRESS RELEASE: Rebiotix and Microbiome Insights collaborate on a microbiome IBD tool for clinical development

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Recent study provides proof of concept for using novel scoring system to define IBD-related changes in microbiome

With a growing body of science linking gut microbiota to inflammatory bowel disease (IBD), a need exists in clinical settings to understand changes in the gut microbial community as they relate to IBD and its management.
Two leading microbiome companies, Rebiotix (part of the Ferring Pharmaceuticals Group) and Microbiome Insights, are collaborating to validate one such tool: a proprietary analysis to determine how closely a patient’s microbiome resembles that of someone with IBD. Microbiome Insights’ bioinformaticians developed an IBD Microbiome Score, based on a vast dataset of over 1600 individuals with IBD and healthy controls. The metric combines the latest understandings of the gut microbiome as a complex ecosystem with information on hundreds of taxa in the bacterial community, rather than the presence or absence of specific taxa. Based on fecal microbial characterization by sequencing, the IBD Microbiome Score can be assigned for each individual patient at diagnosis and at different times throughout treatment, making the Score practical for clinical use. Leveraging Rebiotix’s proprietary Microbiota Restoration Therapy™ (MRT) drug development platform, the Score is being evaluated in active clinical trials to treat IBD.

“The microbiome field is enormously complex,” says Dr. Ken Blount, Rebiotix’s Chief Scientific Officer. “With the use of the first-in-class Rebiotix MRT platform continuing to expand into complex conditions such as IBD, it is critical to have strong, scientifically-validated tools to understand the dynamics of the microbiomes changes within our patients. We’ve seen first-hand how the novel platform and expertise of Microbiome Insights has the potential to rapidly advance not only our understanding of the impact of MRT on patients, but also to uncover valuable microbiome findings for the entire industry.”

“Our scientific team has consulted with leading gastroenterologists to explore ways of leveraging the science on the microbiome and IBD in the clinical setting,” says Microbiome Insights CEO Malcolm Kendall. “Now we have developed the first scientifically robust tool for tracking the microbiome of people with IBD and understanding its link to clinical outcomes. The ability to work with Rebiotix on this path to discovery underscores the future utility of our platform in the clinical setting.”

The companies are continuing to explore applications of Rebiotix interventions and Microbiome Insights’ personal health platform in other microbiome-related diseases.

About Rebiotix
Rebiotix Inc., part of the Ferring Pharmaceuticals Group, is a late-stage clinical microbiome company focused on harnessing the power of the human microbiome to revolutionize the treatment of debilitating diseases using drug products built on its pioneering Microbiota Restoration Therapy™ (MRT) platform. The MRT platform is a standardized, stabilized drug technology that is designed to rehabilitate the human microbiome by delivering a broad consortium of live microbes into a patient’s intestinal tract via a ready-to-use and easy-to-administer format. For more information on Rebiotix and its pipeline of human microbiome-directed therapies, visit www.rebiotix.com.

About Microbiome Insights
Microbiome Insights, Inc. is a global leader providing end-to-end services for microbiome DNA sequencing, including state-of-the-art bioinformatic analysis. Based in Vancouver, Canada, the company’s customized suite of services enables researchers and clinicians to easily and effectively include microbiome analysis in studies across a range of human, animal, agricultural and environmental applications. The multidisciplinary team of researchers and knowledge leaders at the company provide access to decades of expertise in traditional sciences such as ecology, microbiology, infectious diseases, and genetics. Microbiome Insights’ award-winning team is committed to providing clients with fast, dependable, cost-effective results.

See the original Business Wire press release here.

Denise Kelly representing Seventure on what makes a successful microbiome company

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A growing number of start-up microbiome companies—from new players in the established probiotics industry, to university spin-outs focused on novel microbiome-based therapeutics—are looking for support and funding. In this competitive environment, how can a new company make the cut?

For the past several years Professor Denise Kelly has worked with Seventure Partners, a leading European Investor—which has the first venture fund, Health for Life, dedicated to investing in microbiome-focused start-ups, led by Seventure’s CEO, Isabelle de Cremoux. Kelly has participated in panels at both the Translational Microbiome Conference (Boston, USA) and the Global Engage Microbiome Futures event (New York, USA) and recently gave keynote lectures at the IHMC meeting in Killarney and the NeuroCon-X meeting in Prince Edward Island, Canada. Here, Microbiome Insights hears Prof. Kelly’s summary of what will set up a microbiome-based company for success.

Use strong science—and own it

Kelly says Seventure has looked at more than 400 companies in the microbiome sector. The first question she asks is whether the science behind the product or service is robust—a major factor for the Seventure Life Science team. She notes, “We are really fortunate that a lot of interest comes from tier one academics and the findings are published in high-impact journals”—so the science has been peer-reviewed and often validated by independent research, adding to its credibility.

Moreover, Kelly says the strongest scientific ‘package’ combines wetlab work with human studies that address potential mechanisms of action in humans. And she notes that companies generally need to have more than 16S data on hand: “We know so much about strain level impact; shotgun sequencing gets you a lot more information. But even then, the industry is moving towards a multi-omics approach—for example, including metatranscriptomics  and metabolomics, so we know ‘who’ occupies an ecosystem but also what they are doing.”

The next question about the science is whether it’s unique: Do competitors have something similar? Having a strong patent portfolio is crucial as it gives the company a distinct competitive advantage.

Build your revenue stream

Among all the possible life sciences areas in which VCs can invest, microbiome science is still in its early days—meaning they are likely to proceed with caution. Kelly says, “Investing in the ‘discovery’ phase is inherently risky; investors want to see that others have invested in the ideas as well.” She says the solution is to use as many resources as possible to build a company’s revenue space, including building multiple product opportunities and diversifying target disease indications—and importantly, building partnerships and licensing opportunities. Very competitive companies are also winning sizeable non-dilutive grants.

Get your regulatory ducks in a row

The science may look exciting now, but what’s the plan for bringing it to market? Many potential therapeutics in the microbiome area—for example, ‘bugs as drugs’—will face unique regulatory challenges. Kelly recommends connecting with regulatory advisors early on so the company can plan for the realities of getting past the hurdles. And even in cases where the regulatory path for a particular indication is relatively well-established, those at the helm of the company need to understand the complexities of the manufacturing process and how regulatory requirements need to be factored in.

Build relationships strategically

Kelly emphasizes that no successful company is built in a bubble: it needs supporters in order to build success. Companies need relationships with key people in academia and elsewhere—and not just a list of names to put up on the web page, but people who really care about what it’s doing and who are willing to jump in with advice and support.

Kelly says it’s especially important to engage with key opinion leaders (KOLs) with knowledge about the specific indication on which the product is focused. A company that demonstrates authentic engagement with these individuals has a better chance of leading the way in the therapeutic space.

Know when to keep your cards close

As a company is building, it’s important to strategize about how much to reveal—at what times, and to whom. She says, “Approach investors, such as Seventure, when you have a clear vision of your commercial opportunity. Although we invest in early stage start-ups, we appreciate companies that have a strong science package as well as a robust business plan that clearly sells the path to clinic and ultimately, to the marketplace.”

Having all these pieces in place won’t guarantee success—but Kelly says they will certainly make investors take a closer look. “The microbiome industry is moving very fast and the number of new start-ups continues to grow exponentially. At Seventure, we continue to build our portfolio and very recently our CEO, Isabelle de Cremoux, announced the first close of a new AVF fund with Adisseo, dedicated to innovation in Animal Health and Nutrition.”

Without a doubt, the microbiome industry as a whole is truly disruptive and represents a complete paradigm shift in human and animal healthcare. Says Kelly: “We are confronted with numerous modalities, ranging from nutritional products through to microbiome-based drug therapies which can modulate microbiome community function and structure, significantly impacting health status but also disease risk and disease progression. Personalized approaches to medical care are also envisaged, as predictive microbiome biomarkers are being sought—and these could provide more accurate diagnostic and prognostic patient read-outs, leading to more predictable and enhanced drug efficacy. The next five years will be very exciting for many, many reasons. Our knowledge base will continue to grow, but most importantly, we also start to see completion of phase II/III human clinical trials.”

Study led by Afribiota investigators shows stunted growth in children is associated with gastrointestinal ‘de-compartmentalization’

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Stunting, the impaired growth and development of children, affects an estimated 155 million children per year. This represents roughly 25% of the world’s children and there exists a substantial lack of knowledge regarding the underlying causes and potential treatments. Current thinking on stunting hypothesizes that contributing factors such as inadequate psychosocial stimulation, poor nutrition, and recurrent infection are to blame. New research, however, is indicating that the microbial community of the small intestine, an organ essential for digestion and nutrient absorption, may be another contributing factor.

New data, published in PNAS by Afribiota investigators, including Microbiome Insights co-founder Dr. Brett Finlay, found that children suffering from stunting are affected by bacterial overgrowth in the small intestine and possess a microbial community made up from mainly oropharyngeal bacteria. Researchers studied duodenal and gastric samples of children with stunting, aged 2-5 years, in comparison with healthy children living in sub-Saharan Africa. Using 16S Illumina amplicon sequencing and semi-quantitative culturing methods they characterized the microbial communities of these children and found the small intestinal bacterial overgrowth in children with stunting.

The small intestines of children with stunting harboured bacterial species normally found in the oropharyngeal cavity. This overgrowth was also represented in fecal samples from the stunted children—which suggested a path toward developing non-invasive biomarkers for this condition. Furthermore, in stunted children Escherichia coli, Shigella species and Campylobacter species were more prevalent and Clostridia, well-known butyrate producers, were reduced.

These results indicate stunted children are experiencing a de-compartmentalization of the gastrointestinal tract, possibly a result of poor oral hygiene, recurrent or chronic rhino-pharyngeal infections, a hypo-chloric environment in the stomach (which weakens the natural barrier of stomach acidity), or other changes to the stomach environment which reduce its ability to kill unwanted bacteria. Importantly, these changes were seen in two geographically and nutritionally distinct populations, providing strong evidence that bacterial overgrowth is a conserved feature of the stunting condition itself.

The exact role of the oropharyngeal bacteria in intestinal inflammation, while yet to be determined, may provide vital information toward understanding the pathophysiology of stunting and potential new treatments.

Vonaesch P, Morien E, Andrianonimiadana L, et al. Stunted childhood growth is associated with decompartmentalization of the gastrointestinal tract and overgrowth of oropharyngeal taxa. Proc Natl Acad Sci U S A. 2018; 155: E8489-E8498.

PRESS RELEASE: Microbiome Insights receives funding from the Government of Canada to develop new microbiome testing platform for managing chronic disease

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Vancouver, British Columbia (September 12, 2018)—Microbiome Insights, Inc. is pleased to announce that it will receive a contribution of up to $190,249 from the National Research Council of Canada Industrial Research Assistance Program (NRC IRAP) to help support the development of a new personal health platform of microbiome testing.

Co-founded by Drs. Brett Finlay and Bill Mohn at University of British Columbia in 2015, Microbiome Insights is a rapidly growing company and a global leader in microbiome testing and bioinformatic analysis. The advisory services and financial assistance from the Government of Canada, through NRC IRAP, will help the company expand in a new direction—continuing to develop tools for use in clinical settings as new data emerge on the gut microbiome and health.

“We’re leveraging our expertise in microbiome testing to develop a suite of tools for monitoring chronic disease in clinical practice,” says Microbiome Insights CEO Malcolm Kendall. “From the practitioner interface to the educational components of the test, our team is taking a fresh approach that is going to change the game for microbiome testing.”

The primary aim of the company’s personal health platform is to help address the challenges both healthcare practitioners and individuals face in the management of chronic disease.  Microbiome monitoring in those with chronic disease may provide a tool for assessing response to therapies or to various lifestyle changes (including diet), particularly when integrated with robust research findings and ongoing data collection.

The company’s new testing platform will be aimed at health practitioners helping individuals who live with inflammatory bowel disease. The efforts are led by Nataša Jovic, MBA, who brings to the company twenty years of experience in therapeutic and diagnostic commercialization. The company is currently exploring opportunities to commercialize its platform of microbiome tests for healthcare practitioners through research collaborations and distribution or joint commercialization efforts.

See the original BusinessWire press release here.

New paper from Microbiome Insights co-founder on critical window for the gut microbiome in infants and the later occurrence of asthma

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Among serious and chronic childhood diseases, asthma is the most prevalent. Currently there exists no cure for asthma—only treatments designed to help manage symptoms. Recently, a body of research attempting to unravel how this condition develops  in young children has emerged, so that prevention may one day eliminate or reduce the burden of this chronic condition.

Recent work identified the existence of a critical window during the early lives of both mice and children, during which gut microbial changes are associated with the development of asthma. This provided an avenue to explore the role of the gut microbiome during early childhood development and the onset of chronic diseases like asthma. Importantly though, we know the gut microbiome varies greatly among those raised in different geographic regions. Therefore, understanding how changes in gut microbiota related to asthma development differ globally may provide valuable insights into the mechanism of asthma development.

A new paper, led by Microbiome Insights co-founder Brett Finlay and published in The Journal of Allergy and Clinical Immunology, evaluated the associations of fungal and bacterial changes (dysbiosis) in infants raised in the non-industrialized setting of rural Ecuador. The research was conducted as a collaboration between members of the Universities of British Colombia and Calgary, the BC Children’s Hospital, and Universidad Internacional del Ecuador. Children with atopic wheeze (27 in total) along with 70 healthy controls were identified and their bacterial and eukaryotic gut microbiota analysed at age 3 months. Stool samples were collected and sequencing of the 16S and 18S regions predicted bacterial metagenomes while fecal short chain fatty acids were determined via gas chromatography.

Results indicated that, similar to the previous findings in Canadian children, microbial dysbiosis in Ecuadorian infants at 3 months was associated with the subsequent development of atopic wheeze. Surprisingly though, the dysbiosis observed in Ecuador involved different bacteria taxa as well as some fungal species, and this was more pronounced than in Canada. Some predictions based on the metagenome analysis also emphasized significant dysbiosis-associated differences in genes involved in carbohydrate and taurine metabolism. The fecal short-chain fatty acid acetate was reduced while caproate was increased in children at 3 months who later developed atopic wheeze.

This work continues to provide evidence that there is a critical window during the first 100 days of life during which microbial dysbiosis is strongly associated with development of atopic wheeze. The study also yielded several valuable pieces of information. Despite the involvement of different bacteria taxa, both the Canadian and Ecuadorian populations had decreased fecal acetate, suggesting alterations to fermentation patterns may be a common factor associated with atopic wheeze. Furthermore, the pronounced role of fungal dysbiosis in this study led researchers to recommend that “the role of P. kudriavzevii and other yeasts should be explored in mechanistic studies using animal models.”

Along with more studies characterizing the early microbiome in more communities around the world, optimized biomarker studies of microbial taxa and metabolites could lead to better predictions of risk and therapeutic strategies to restore gut microbial health as a prevention method.

 

How Microbiome Insights can help with your Canadian microbiome research grant application

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Competition for funding can be tough—but if you’re applying to a Canadian granting agency to fund a microbiome study, the Microbiome Insights team will be pleased to help. Some granting agencies require you to name an industry partner—and as the leading Canadian industry partner dedicated to microbiome testing and bioinformatic analysis, we are positioned to help your application be as successful as possible.

Here are some frequently asked questions about how we can help with microbiome research grant applications in Canada.

What kinds of testing does Microbiome Insights do?

Microbiome Insights has a full suite of sequencing options—some of which may not be readily available at your own institution. Our services include amplicon sequencing (16S V4, 16S V1-V3, 16S V4_skin, 18S, ITS2 and Archaeal V4-V5), shotgun metagenomics, and bacterial whole genome sequencing; in addition to sequencing we run short-chain fatty acid analyses and calprotectin testing. If these are relevant to your research, please contact us for more information on pricing, turnaround time, and support. Feel free to include our details in your grant application to show you’ve got everything lined up and ready to go for your research.

How flexible are the services?

While an end-to-end service is appealing to some, it doesn’t suit everyone. We can provide the full end-to-end service if needed or we can provide only the parts that make sense to you: for example, if you’re interested in learning more about bioinformatics yourself, you can obtain raw data from our team and explore the data on your own. Under this model, you’ll be able to leverage our wet lab standards while continuing to grow your own understanding of the microbiome.

Everything we do it price sensitive, so we have the ability charge per sample rather than having you lock into a full plate or a full run.

How can partnering with Microbiome Insights make the grant application stronger?

Including us in your grant applications shows you have strong collaborators and leading expertise on your side, bridging to the knowledge of our team and our co-founders (Drs. Brett Finlay and Bill Mohn). Through us, you’ll be able to secure expertise and support in the areas where you need it, and you’ll be able to access industry standards and proven pipelines. Moreover, you can be assured that all of this is done in Canada, with leading Canadian experts in the field.

What specific assistance can the Microbiome Insights team offer for grant applications?

We’ll consult with you to better understand (and draft, if necessary) the study design. We can give you guidelines on collection and transport to insert into your application, and can provide a mock report of the results if required. Our team members can also be hired to write a detailed results or methods section for your application.

Most importantly, we also offer a letter of support which details your study objectives, our deliverables for services and reporting, along with workflows and pricing. These details are key features of your submission, and we are always able to edit the details as funding is released.

How many Microbiome Insights clients come from academia?

The majority of our clients at present come from academia and publish their results in leading journals. If you choose to partner with us, you’ll have access to the same exceptional team that’s used by well-known researchers worldwide.

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